1. Field of Invention
This invention relates generally to non-pharmacologic adjunct (add-on) treatment for pain, more specifically to adjunct treatment of pain by modulating electrical signals to a selected nerve or nerve bundle utilizing an easily implanted lead-receiver and an external stimulator.
2. Background
Analgesia by neural stimulation, either transcutaneously or through inserted needles (electro-acupuncture), has been demonstrated in humans. In the transcutaneous electrical nerve stimulation (TENS) method (such as with a device manufactured by Xytron Medical), two standard carbon rubber electrodes with gel are fixed on patient's skin across the tissue to be stimulated. One electrode being the negative pole and other being the positive pole. Utilizing the two electrodes, asymmetric biphasic pulses are used, with the frequency and pulse width being adjustable. Because the skin has high impedance, relatively large outputs are required to stimulate, and the site to be stimulated is not very specific. Other tissues including muscle, between the two skin electrodes will be stimulated.
Another method of stimulating a nerve is by using a percutaneous needle, or a lead with one end (distal end) being next to the nerve and utilizing a patch somewhere on the skin as the return electrode. Such a method is not feasible for long term stimulation because of the potential for infection, but can be useful for short term testing.
The time course and the distribution of the analgesic effect vary with the stimulus frequency used. The analgesic effect of high-frequency (40-400 Hz), low-intensity stimulation is largely confined to the spinal segment stimulated and the effect has a relatively short time course. The response is explained by events at the level of the spinal cord, as expressed in the spinal gate-control theory, which suggests an inhibition of cells transmitting information from nociceptors (receptors for pain) by activation of low-threshold afferents. Analgesia by low-frequency (2-5 Hz) peripheral stimulation is characterized by a slower time course with a long induction time (15-30 min.) and an effect outlasting the stimulation period from 20 min. to several hours. Furthermore, the effect is widespread and not confined to the spinal segment being stimulated. This suggests a different, presumably humoral mechanism, possibly due to b-endorphin. This slow time course is not only found with low-frequency peripheral nerve stimulation but also with classical needle acupuncture. The two modes of stimulation are assumed to act through similar mechanisms.
To understand the basics, it is instructive to see what happens when one accidentally hits their thumb with a hammer. A common sequence is to withdraw the thumb, yell (via limbic connections), and then apply pressure to the injured thumb. The first scientific explanation of how pressure and other external stimuli inhibit pain transmission was the gate theory of pain, proposed by Melzack and Wall in 1965. They hypothesized that information from first-order low-threshold mechanical afferents and from first-order nociceptive afferents converges into the same second-order neurons. They proposed that the preponderance of activity in the primary afferents determines the pattern of signals the second-order neuron transmits. Thus, if the low-threshold mechanical afferents are more active than the nociceptive afferents, the mechanoreceptive information is transmitted and the nociceptive information inhibited. According to their theory, transmission of pain information is blocked in the dorsal horn, closing the gate to pain. Lamina II, the substantia gelatinsosa, was suggested as the site of interference with pain massage transmission. The gate theory is important because it inspired inquiry into the mechanics and control of pain. One result of these investigations was the clinical application of transcutaneous electrical nerve stimulations (TENS). TENS uses electrical current applied to the skin to interfere with the transmission of pain information.
Another theory that has incorporated findings from research stimulated by the gate theory is the counterirritant theory. According to the counterirritant theory, inhibition of nociceptive signals by stimulation of non-nociceptive receptors occurs in the dorsal horn of the spinal cord, as shown in FIG. 1 (from: Neuroscience-Fundamentals for Rehabilitation, Page 119. W. B. Saunders Company).
For example, as shown in FIG. 1, pressure stimulates mechanoreceptive afferents 24. Theoretically, proximal branches of the mechanoreceptive afferents 24 activate interneurons 22 that release the neurotransmitter enkephalin. Enkephalin binds with receptor sites on both the primary afferents and interneurons 22 of the pain system. Enkephalin binding depresses the release of substance P and hyperpolarizes the interneurons 22, thus inhibiting the transmission of nociceptive signals to the spinothalamic tract 27. FIG. 1 also shows tissue damage 25 and a pathway to the dorsal column 26.
Most nerves in the human body are composed of thousands of fibers, of different sizes designated by groups A, B and C, which carry signals to and from the brain. The vagus nerve, for example, may have approximately 100,000 fibers of the three different types, each carrying signals. Each axon (fiber) of that nerve conducts only in one direction, in normal circumstances. The A and B fibers are myelinated (i.e., have a myelin sheath, constituting a substance largely composed of fat), whereas the C fibers are unmyelinated.
A commonly used nomenclature for peripheral nerve fibers, using Roman and Greek letters, is given in the table below,
External Conduction Diameter Velocity Group (.mu.m) (m/sec) Myelinated Fibers A.alpha. or IA 12-20 70-120 A.beta.:IB 10-15 60-80 II 5-15 30-80 A.gamma. 3-8 15-40 A.delta. or III 3-8 10-30 B 1-3 5-15 Unmyelinted fibers C or IV 0.2-1.5 0.5-2.5
The diameters of group A and group B fibers include the thicknesses of the myelin sheaths. Group A is further subdivided into alpha, beta, gamma, and delta fibers in decreasing order of size. There is some overlapping of the diameters of the A, B, and C groups because physiological properties, especially the form of the action potential, are taken into consideration when defining the groups. The smallest fibers (group C) are unmyelinated and have the slowest conduction rate, whereas the myelinated fibers of group B and group A exhibit rates of conduction that progressively increase with diameter. Group B fibers are not present in the nerves of the limbs; they occur in white rami and some cranial nerves. Myelinated fibers are typically larger, conduct faster and have very low stimulation thresholds, compared to the unmyelinated type, and exhibit a particular strength-duration curve or respond to a specific pulse width versus amplitude for stimulation. The A and B fibers can be stimulated with relatively narrow pulse widths, from 50 to 200 microseconds (.mu.s), for example. The A fiber conducts slightly faster than the B fiber and has a slightly lower threshold. The C fibers are very small, conduct electrical signals very slowly, and have high stimulation thresholds typically requiring a wider pulse width (300-1,000 .mu.s) and a higher amplitude for activation.
The vagus nerve is composed of somatic and visceral afferents (i.e., inward conducting nerve fibers which convey impulses toward the brain) and efferents (i.e., outward conducting nerve fibers which convey impulses to an effector). Usually, nerve stimulation activates signals in both directions (bi-directionally). It is possible, however, through the use of special electrodes and waveforms, to selectively stimulate a nerve in one direction only (unidirectionally). The vast majority of vagal nerve fibers are C fibers, and a majority are visceral afferents having cell bodies lying in masses or ganglia in the skull. The central projections terminate largely in the nucleus of the solitary tract which sends fibers to various regions of the brain, e.g., the hypothalamus, thalamus, and amygdala. Most authorities believe that pain is recognized or perceived in the thalamus.
The most commonly experienced form of pain may be defined as the effect of a stimulus on nerve endings, which results in the transmission of impulses to the cerebrum. In an ascending pathway, the axons travel in the spinothalamic tract upward to the thalamus where they synapse on third order neurons in the ventral posterolateral nucleus of the thalamus or posteromedial, for sensation from the face. The pain sensations are usually carried by small diameter A.delta. fibers or C fibers.
There is also a descending pathway which inhibits the incoming pain signals, and is therefore important on the body's endogenous control of pain. This system includes the periaqueductal grey, the dorsal raphe nuclei, locus ceruleus, and nuclei of the medullary reticular formation. The nuclei send descending axons in the dorsolateral funiculus and synapse in the dorsal horn of the spinal cord. Spontaneous activation of these pathways, some of which involve activation of endogenous opiate system, tends to suppress pain transmission.
Observations on the profound effect of electrical stimulation of the vagus nerve on central nervous system (CNS) activity, extends back to 1930's. Intermittent vagal stimulation has been relatively safe and well tolerated. The minimal side effects of tingling sensations and brief voice abnormalities have not been distressing. The vagus nerve provides an easily accessible, peripheral route to modulate central nervous system (CNS) function. Other cranial nerves can be used for the same purpose, but the vagus nerve is preferred because of its easy accessibility. In the human body there are two vagal nerves (VN), the right VN and the left VN. Each vagus nerve is encased in the carotid sheath along with the carotid artery and jugular vein. The innervation of the right and left vagal nerves is different. The innervation of the right vagus nerve is such that stimulating it results in profound bradycardia (slowing of the heart rate). The left vagal nerve has some innervation to the heart, but mostly innervates the visceral organs such as the gastrointestinal tract. It is known that stimulation of the left vagal nerve does not cause any significant deleterious side effects.
The basic premise of vagal nerve stimulation is that vagal visceral afferents have a diffuse central nervous system (CNS) projection, and activation of these pathways has a widespread effect on neuronal excitability. The cervical component of the vagus nerve (10.sup.th cranial nerve) transmits primarily sensory information that is important in the regulation of autonomic activity by the parasympathetic system. General visceral afferents constitute approximately 80% of the fibers of the nerve, and thus it is not surprising that vagal stimulation (VS) can profoundly affect CNS activity. With cell bodies in the nodose ganglion, these afferents originate from receptors in the heart, aorta, lungs, and gastrointestinal system and project primarily to the nucleus of the solitary tract which extends throughout the length of the medulla oblongata.
Activation of the descending anti-nociceptive pathway by stimulation of vagal afferents is, in many instances, an appropriate strategy for treatment of chronic pain of neuropathic or psychogenic origin, especially pain which is intractable to drug therapy.
U.S. Pat. No. 3,796,221 (Hagfors) is directed to controlling the amplitude, duration and frequency of electrical stimulation applied from an externally located transmitter to an implanted receiver by inductively coupling. Electrical circuitry is schematically illustrated for compensating for the variability in the amplitude of the electrical signal available to the receiver because of the shifting of the relative positions of the transmitter-receiver pair. By highlighting the difficulty of delivering consistent pulses, this patent points away from applications such as the current application, where consistent therapy may need to be continuously sustained over a prolonged period of time. The methodology disclosed is focused on circuitry within the receiver, which would not be sufficient when the transmitting coil and receiving coil assume significantly different orientation, which is likely in the current application. The present invention discloses a novel approach for this problem, using "targets" located in the external patch electrode. Additionally, the mode of stimulation in Hagfors patent is "bipolar" whereas in the current patent, the mode of stimulation is "unipolar" i.e. between the tip electrode and case.
U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807 (Zabara) generally disclose animal research and experimentation related to epilepsy and the like and are directed to stimulating the vagas nerve by using pacemaker technology, such as an implantable pulse generator. These patents are based on several key hypotheses, some of which have since been shown to be incorrect. The pacemaker technology concept consists of a stimulating lead connected to a pulse generator (containing the circuitry and DC power source) implanted subcutaneously or submuscularly, somewhere in the pectoral or axillary region, with an external personal computer (PC) based programmer. Once the pulse generator is programmed for the patient, the fully functional circuitry and power source are fully implanted within the patient's body. In such a system, when the battery is depleted, a surgical procedure is required to disconnect and replace the entire pulse generator (circuitry and power source). These patents neither anticipate practical problems of an inductively coupled system nor suggest solutions to the same for an inductively coupled system. FIG. 4 in all three above Zabara patents show the stimulation electrode around the right vagus nerve. It is well known that stimulation of right vagus can lead to profound bradycardia (slowing of the heart rate), an unwanted complication.
U.S. Pat. No. 5,330,515 (Rutecki et al.) is directed to the use of pacemaker technology for vagal nerve stimulation for treating and controlling pain. Pacemaker technology consists of an implantable pulse generator and lead, and an external PC based programmer. This patent does not suggest solutions to the issues and problems of an inductively coupled system.
U.S. Pat. No. 5,031,618 (Mullett) discloses a position sensor for chronically implanted neuro stimulator for stimulating the spinal cord. The position sensor, located in a chronically implanted programmable spinal cord stimulator, modulates the stimulation signals depending on whether the patient is erect or supine.
U.S. Pat. No. 4,573,481 (Bullara) is directed to an implantable helical electrode assembly configured to fit around a nerve. The individual flexible ribbon electrodes are each partially embedded in a portion of the peripheral surface of a helically formed dielectric support matrix.
U.S. Pat. No. 3,760,812 (Timm et al.) discloses nerve stimulation electrodes that include a pair of parallel spaced apart helically wound conductors maintained in this configuration.
U.S. Pat. No. 4,979,511 (Terry) discloses a flexible, helical electrode structure with an improved connector for attaching the lead wires to the nerve bundle to minimize damage.
An implantable pulse generator and lead with a PC based external programmer is advantageous for cardiac pacing applications for several reasons, including:
1) A cardiac pacemaker must sense the intrinsic activity of the heart, because cardiac pacemakers deliver electrical output primarily during the brief periods when patients either have pauses in their intrinsic cardiac activity or during those periods of time when the heart rate drops (bradycardia) below a certain pre-programmed level. Therefore, for most of the time, in majority of patients, the cardiac pacemaker "sits" quietly monitoring the patient's intrinsic cardiac activity.
2) The stimulation frequency for cardiac pacing is typically close to 1 Hz, as opposed to approximately 20 Hz or even significantly higher, typically used in nerve stimulation applications such as pain control.
3) Patients who require cardiac pacemaker support are typically in their 60's, 70's or 80's years of age.
The combined effect of these three factors is that the battery in a pacemaker can have a life of 10-15 years. Most patients in whom a pacemaker is indicated are implanted only once, with perhaps one surgical pulse generator replacement.
In contrast, patients with intractable pain in whom electrical stimulation is beneficial can be younger as a group. Also, stimulation frequency is typically 20 Hz and can be much higher, and the total stimulation time per day is much longer than for cardiac pacemakers. As a result, battery drain is typically much higher for nerve stimulation applications than for cardiac pacemakers.
The net result of these factors is that the battery will not last nearly as long as in cardiac pacemakers. Because the indicated patient population can also be much younger, the expense and impact of surgical generator replacement will become significant, and detract from the appeal of this therapy. There are several other advantages of the present inductively coupled system.
1) The hardware components implanted in the body are much less. This is advantageous for the patient in terms of patient comfort, and it decreases the chances of the hardware getting infected in the body. Typically, when an implantable system gets infected in the body, it cannot be easily treated with antibiotics and eventually the whole implanted system has to be explanted.
2) Because the power source is external, the physician can use stimulation sequences that are more effective and more demanding on the power supply.
3) With the controlling circuitry being external, the physician and the patient may easily select from a number of predetermined programs, or manually operate the device. The predetermined programs can even be modified.
4) The external inductively-coupled nerve stimulation (EINS) system is quicker and easier to implant.
5) The external pulse generator does not need to be monitored for "End-of-Life" (EOL) like the implantable system, thus resulting in cost saving and convenience.
6) The EINS system can be manufactured at a significantly lower cost than an implantable pulse generator and programmer system, providing the patient and medical establishment with cost effective therapies.
7) The EINS system makes it more convenient for the patient or caretaker to turn the device on demand for "as need" type of application.
8) Occasionally, an individual responds adversely to an implanted medical device and the implanted hardware must be removed. In such a case, a patient having the EINS systems has less implanted hardware to be removed and the cost of the pulse generator does not become a factor.
In the conventional manner of implanting, a cervical incision is made above the clavicle, and another infraclavicular incision is made in the deltapectoral region for the implantable stimulus generator pocket. To tunnel the lead to the cervical incision, a shunt-passing tool is passed from the cervical incision to the generator pocket, where the electrode is attached to the shunt-passing tool and the electrode is then "pulled" back to the cervical incision for attachment to the nerve. This standard technique has the disadvantage that it is time consuming and it tends to create an open space in the subcutaneous tissue. Post surgically the body will fill up this space with serous fluid, which can be undesirable.
To make the subcutaneous tunneling simpler and to avoid possible complication, one form of the implantable lead body is designed with a hollow lumen to aid in implanting. In this embodiment, a special tunneling tool slides into a hollow lumen. After the cervical and infraclavicular incisions are made, the tunneling tool and lead are simply "pushed" to the cervical incision and the tunneling tool is pulled out. Since the tunneling tool is inside the lead, no extra subcutaneous space is created around the lead, as the lead is pushed. This promotes better healing post-surgically.
The apparatus and methods disclosed herein also may be appropriate for the treatment of other conditions, as disclosed in co-pending applications filed on Oct. 26, 1998, entitled APPARATUS AND METHOD FOR ADJUNCT (ADD-ON) THERAPY OF PARTIAL COMPLEX EPILEPSY, GENERALIZED EPILEPSY AND INVOLUNTARY MOVEMENT DISORDERS UTILIZING AN EXTERNAL STIMULATOR and APPARATUS AND METHOD FOR ADJUNCT (ADD-ON) THERAPY OF DEMENTIA AND ALZHEIMER'S DISEASE UTILIZING AN IMPLANTABLE LEAD AND AN EXTERNAL STIMULATOR, the disclosures of which are incorporated herein by reference.